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Biomedical subjects

M Burt

Publications and source records attributed to M Burt.

At least 37 records · Page 2Linked to original sources

Metastatic adenocarcinoma involving a mesothelial/monocytic incidental cardiac excrescence (cardiac MICE)

Mesothelial/monocytic incidental cardiac excrescence (MICE) is a recently described, peculiar microscopic finding in the endocardium or pericardium. These lesions are characterized by a mixture of mesothelial cell clusters and histiocytes, aggregated by fibrin. They have been interpreted as reactive or even artifactual, and the importance of distinguishing these aggregations from metastatic carcinoma has been emphasized. We report a unique case of a MICE that was seeded by clusters of metastatic adenocarcinoma cells. The patient was a 38-year-old woman with no history of previous cardiac instrumentation who was found to have an adenocarcinoma of the right lung involving the hilus but apparently not invading the pericardium. At surgery, a small fragment of tissue was found floating in the pericardial cavity, and microscopic examination revealed a cluster of histiocytes, mesothelial cells and fibrin (components of usual, benign MICE) in which rare pleomorphic adenocarcinoma cells were scattered. Unlike the surrounding mesothelial cells and histiocytes, the pleomorphic cells stained for carcinoembryonic antigen, epithelial membrane antigen, and BerEP4 and focally produced intracellular mucin, confirming their malignant glandular nature. It is possible that the surrounding mesothelial cells, histiocytes, and fibrin were formed in response to invasion of the pericardial space by adenocarcinoma. This case indicates that not all lesions with the characteristic architecture of MICE can be dismissed as non-neoplastic without careful evaluation of both the cellular constituents and the clinical circumstances.

Adenocarcinoma↗

Comparison of two algorithms and their associated charges when evaluating adrenal masses in patients with malignancies.

OBJECTIVE: This study was performed to compare two proposed algorithms used when evaluating an adrenal mass discovered during staging evaluation of a patient with a known malignancy. Such evaluation was meant to lead to determination of the relative charges associated with each algorithm. SUBJECTS AND METHODS: Fifty-four patients with known malignancies who required evaluation of an adrenal mass underwent both chemical shift imaging (CSI) and CT-guided for CSI. The hospital charges incurred for each procedure and any associated complications were normalized using national relative-value scale charges and conversion factors. A decision analysis was performed to compare the relative charges that would have been incurred if adrenal MR imaging had been performed in all patients, followed by CT-guided biopsy only in those patients with MR findings not diagnostic of adrenocortical adenoma, and the relative charges incurred if only CT-guided adrenal biopsy had been performed in every patient. RESULTS: Twenty-three (43%) of 54 adrenal masses were shown to be metastases by CT-guided biopsy. The sensitivity and specificity of CSI for the diagnosis of adrenocortical adenoma were 94% and 100%, respectively. The charges incurred by performing MR imaging as the initial examination with subsequent CT-guided biopsy only in those patients with CSI findings not diagnostic of adenoma would have been similar to those incurred by first performing CT-guided adrenal biopsy in every patient. CONCLUSION: CSI is an accurate, noninvasive technique for evaluating adrenal masses in patients with cancer. If CT-guided biopsy is used only when CSI is not diagnostic of adrenocortical adenoma, the associated charges would be virtually the same as when CT-guided biopsy is performed as the first test in every patient. Moreover, biopsies could have been avoided in 54% of these patients.

Adrenal Cortex Neoplasms↗

Detection of circulating donor deoxyribonucleic acid by microsatellite analysis in a liver transplant recipient.

The diagnosis of graft-versus-host disease following liver transplantation may be delayed because the clinical and pathological features are nonspecific. We report the use of microsatellites to support a diagnosis of GVHD in a patient who developed fever and a skin rash 28 days after liver transplantation. The pattern of microsatellite alleles amplified from the peripheral blood on day 51 posttransplant indicated that recipient and donor DNA were present in approximately equal proportions. Microsatellite typing is a simple and rapid method to identify high levels of circulating donor DNA to support a diagnosis of GVHD following liver transplantation.

Alleles↗

Effect of human growth hormone on human pancreatic carcinoma growth, protein, and cell cycle kinetics.

The role of human growth hormone (hGH) as a nutritional adjunct for cancer patients is controversial because of its potential mitogenic effects on tumor growth. No studies to date have examined the effect of hGH on human tumor response in vivo. In Vitro: Athymic mice were injected (s.c.) daily with hGH (GH, n=14) or saline (CTL, n=14). On Day 10, serum was collected and added to human pancreatic carcinoma cells in culture. In Vivo: Athymic mice were inoculated (s.c.) with human pancreatic carcinoma cells. On Day 14, mice were randomized to receive daily either hGH (GH, n=14) or saline (CTL, n=12). On Day 29, animals received [3H]phenylalanine for tissue protein fractional synthetic rate (FSR) measurement. Tumors were excised and cell cycle kinetics analyzed. Data are expressed as mean +/- SEM. Statistical analysis was performed by unpaired t test and/or ANOVA where appropriate. In Vitro: Serum from GH-treated animals had elevated IGF-1 levels (287 +/- 34 ng/ml vs 157 +/- 53 ng/ml, P<0.001) and significantly stimulated cell growth (No. cells x 10(3)/well) compared with CTL serum (925 +/- 31 vs 747 +/- 38, P<0.001). In Vivo: Serum for GH-treated animals had elevated IGF-1 levels (287 +/- 34 ng/ml vs 157 +/- 53 ng/ml, P<0.001) and significantly stimulated cell growth (No. cells x 10(3)/well) compared with CTL serum (925 +/- 31 vs 747 +/- 38, P<0.001). In Vivo: Growth hormone had no significant effect on tumor growth rate (mm3/day) (1.45 +/- 0.47 CTL vs 1.57 +/- 0.66 GH), final tumor weight (mg) (0.19 +/- 0.15 CTL vs 0.17+/- 0.06 GH), DNA Index (1.5 +/- 0.1 CTL vs 1.5 +/- 0.1 GH), percent S phase (20.3 +/- 3.3 CTL vs 22.1 +/- 3.0 GH), or tumor FSR (%/day) (51.1 +/- 17.8 CTL vs 70.2 +/- 61.1 GH). Growth hormone significantly elevated serum IGF-1 levels (ng/ml) (176 +/- 48 CTL vs 222 +/- 53 GH, P<0.005) and liver FSR (%/day) (62.8 +/- 17.8 CTL vs 79.7 +/- 12.7 GH, P<0.005). Serum of GH-treated mice increased human pancreatic cell growth in vitro. In vivo, GH administration raised serum IGF-1 levels and increased liver protein FSR, without tumor growth, cell cycle kinetics, or protein FSR.

Animals↗

Selective glutathione repletion with oral oxothiazolidine carboxylate (OTZ) in the radiated tumor-bearing rat.

Oxothiazolidine carboxylate (OTZ) is a cysteine prodrug which augments intracellular glutathione (GSH) levels. We examined the effects of oral OTZ on tumor and host tissue reduced GSH levels in fasting and radiated models of GSH depletion. In addition, we studied the tumor's ability to utilize OTZ via the enzyme, oxoprolinase. Fischer 344 rats (n = 40) were implanted with MCA sarcoma and studied at 10% tumor burden. Treatment consisted of 10 mmol/kg OTZ or buffer orally. After a 24-hr fast, 16 animals were treated and tumor, kidney, jejunal, and colonic mucosa were collected after 4 hr. Significant increases in GSH with OTZ (n = 8) vs buffer (n = 8) were seen in kidney (5.6 +/- 0.4 vs 4.3 +/- 0.9; P < 0.01), jejunum (13.8 +/- 1.3 vs 12.1 +/- 1.1; P < 0.05), and colon (6.7 +/- 1.2 vs 5.3 +/- 0.6; P < 0.05), but not tumor (8.9 +/- 2.4 vs 10.6 +/- 1.4; P = 0.12). Sixteen animals were treated 4 hr before and 18 hr following 1100 cGy of abdominal radiation and at 4 days, tumor, jejunal, and colonic mucosa were collected. Significant increases in GSH with OTZ (n = 8) vs buffer (n = 8) were noted in jejunum (9.3 +/- 1.1 vs 7.5 +/- 1.8; P < 0.05) and colon (5.6 +/- 1.1 vs 4.3 +/- 0.9; P < 0.05) but not tumor (8.4 +/- 1.6 vs 7.6 +/- 1.4; P = 0.34). To determine tissue oxoprolinase activity, tumor, kidney, liver, jejunal, and colonic mucosa were collected from 8 animals. Oxoprolinase activity was highest in the kidney (814 +/- 145) with no difference noted between liver and tumor (280 +/- 117 and 324 +/- 137, respectively). Oral OTZ selectively increases reduced GSH levels in normal tissues compared to tumor following fasting and whole abdominal radiation. This increase does not appear to be due to a differential activity of oxoprolinase. OTZ may have a role in protection against toxicity associated with oxidative injury by selective repletion of normal host tissue GSH levels.

Administration, Oral↗

Radiation-associated malignant tumors of the chest wall.

BACKGROUND: Malignant postirradiation cancers of the chest wall are uncommon, and data concerning results of treatment are sparse. We assessed patient characteristics as well as prognostic factors of these tumors compared with those arising de novo and analyzed treatment results of both groups. METHODS: Records of 361 patients with primary malignant tumors of the chest wall admitted to our institution between 1949 and 1989 were reviewed retrospectively. Previous radiotherapy to the site of the tumor was noted with latency period and dose. Survival was calculated via the Kaplan-Meier method, and comparisons of survival were made by log-rank analysis. RESULTS: In 351 patients with primary malignant tumors of the chest wall, 21 lesions (6%) arose in an irradiated field. Eighty-eight patients had chondrosarcoma (age range 5-86 years, median 49; male:female [M:F] ratio 1.3:1), two cases of which arose in an irradiated field; 38 patients had osteosarcoma (age range 11-78 years, median 42; M:F ratio 1.5:1), 11 cases (29%) of which arose in an irradiated field; 149 patients had soft-tissue sarcoma (age range 1-86 years, median 38; M:F ratio 2:1) seven cases (5%) of which arose in an irradiated field; 52 patients had Ewing's sarcoma (age range 2-39 years, median 16; M:F ratio 1.6:1) no cases of which arose in an irradiated field; and 24 patients had a solitary plasmacytoma (age range 37-75 years, median 59; M:F ratio 2.4:1) one case (5%) of which arose in an irradiated field. Prior radiotherapy had been performed for Hodgkin's disease (n = 8), breast cancer (n = 5), and various other indications (n = 8). The maximum radiation dose administered ranged from 1,250 to 9,500 cGy (median 4,140). The latency period from previous irradiation to diagnosis ranged from 2 to 19 years (median 7). The primary therapy of all radiation-associated tumors was resection, except for three patients. There was no significant difference in survival between those malignant chest wall tumors arising in an irradiated field compared with those arising de novo. CONCLUSIONS: Twenty-nine percent of patients with primary osteosarcoma and 2-5% of patients with primary chondrosarcoma, soft-tissue sarcoma, or plasmacytoma of the chest was seen at this institution have a tumor arising in the field of prior irradiation. Because the outcome after operative therapy appears to be similar, these patients should be offered identical treatment to those whose tumors arise de novo.

Adolescent↗

Erythromycin stimulates gastric emptying after esophagectomy with gastric replacement: a randomized clinical trial.

UNLABELLED: Delayed gastric emptying after esophagogastrectomy can pose a significant early postoperative problem. Because erythromycin, which stimulates the gastric antral and duodenal motilin receptor, has been shown to significantly increase gastric emptying in patients with diabetic gastroparesis, we decided to evaluate its effect on gastric emptying after esophagogastrectomy. METHODS: Twenty-four patients (18 men and six women, age range 41 to 79 years, median 66 years) were randomized to receive either erythromycin lactobionate (200 mg in 50 ml normal saline solution intravenously) (n = 13) or placebo (50 ml normal saline solution intravenously (n = 11) 11 days after esophagogastrectomy (with pyloric drainage procedure). After erythromycin or placebo had been infused over a 15-minute period, patients ingested a solid meal (scrambled egg with bread) labeled with technetium 99m sulfur colloid (500 microCi) over approximately 15 minutes. Dynamic images of the stomach were then acquired over 90 minutes in the supine position by gamma imaging. Results were expressed as percentage of counts retained in the stomach (percent gastric retention) over time. RESULTS: There were no side effects of erythromycin. In the placebo group, the mean percent of radiolabeled meal retained in the stomach after 90 minutes was 88%, which was significantly greater than in the erythromycin group, 37% (p < 0.001). In addition, analysis of covariance demonstrated that the rate of gastric emptying (slope of the line) was significantly greater in the erythromycin-treated group than in the placebo group (p < 0.0001). CONCLUSION: Early satiety after esophagogastrectomy may be due to delayed gastric emptying and not due to a decrease in the gastric reservoir. Intravenous erythromycin significantly improves gastric emptying in patients after esophagogastrectomy by stimulating gastric motility.

Adult↗

Depletion of high energy phosphate compouds in the tumor-bearing state and reversal after tumor resection.

BACKGROUND: Cancer cachexia is a syndrome manifested by a variety of metabolic abnormalities that include depletion of host energy stores. We studied liver and skeletal muscle high energy phosphate compounds, inorganic phosphorus (Pi), and the energy charge in tumor-bearing (TB), pair fed non-tumor-bearing (NTB), and tumor-bearing resected (RES) rats. METHODS: F344 rats were randomized into TB (n = 13), NTB (n = 13), and RES (n = 5) groups. On day 0, the flanks of the TB and RES animals were injected with 1 x 10(7)n methylcholanthrene (MCA)-induced sarcoma cells. On day 19, TB and NTB rat liver and skeletal muscle were analyzed for adenine nucleotides, phosphocreatine, and Pi, and RES animals underwent tumor resection followed by tissue analysis 10 days later. RESULTS: Although the liver adenylate energy charge was maintained, the level of liver adenosine monophosphate was significantly increased and the liver adenosine diphosphate level was decreased in the TB animals (3.55 +/- 0.6, 3.70 +/- 0.3 mumoles/gm dry weight, p < 0.05, p = 0.05, respectively) when compared with the NTB animals (3.06 +/- 0.4, 4.00 +/- 0.5 mumoles/gm dry weight, respectively). Muscle adenosine diphosphate levels were significantly decreased in the TB animals (1.57 +/- 0.7 mumoles/gm dry weight) as compared with NTB animals (2.23 +/- 0.7 mumoles/gm dry weight, p < 0.05). In addition, muscle adenosine triphosphate, phosphocreatine, and phosphocreatine/adenosine triphosphate ratios were significantly decreased in TB animals (19.94 +/- 4.5, 81.51 +/- 12.8, and 4.20 +/- 0.8 mumoles/gm dry weight, respectively) as compared with NTB animals (24.44 +/- 1.9, 116.72 +/- 7.5, and 4.81 +/- 0.4 mumoles/gm dry weight, respectively, p < 0.05) and RES animals (24.08 +/- 3.3, 124.10 +/- 12.2, and 5.19 +/- 0.5 mumoles/gm dry weight, respectively, p < 0.05). CONCLUSIONS: These alterations in high energy phosphate compounds in liver and skeletal muscle indicate that although the energy charge is maintained, energy depletion occurs early in the tumor-bearing state. These changes are tumor specific, not related to anorexia, and revert to non-tumor-bearing levels after tumor resection.

Adenosine Triphosphate↗

Inferior vena cava filters in cancer patients: indications and outcome.

PURPOSE: Our experience with inferior vena cava (IVC) filter placement to prevent pulmonary emboli (PE) in cancer patients with deep vein thromboses (DVT) was reviewed to identify indications, patient characteristics, complications, and long-term outcome. METHODS: Charts of 182 patients with cancer were retrospectively analyzed. All patients had received an IVC filter in our institution between January 1980 and April 1992. RESULTS: Of 182 patients, 103 were men and 79 were women. Median age was 59 years (range, 15 to 88). Eight patients (4%) had stage I disease, 22 patients (12%) stage II, 37 patients (20%) stage III, and 115 patients (63%) stage IV. A DVT was diagnosed in 97 patients (53%), a PE in 46 patients (25%), and a combination in 39 patients (21%). Indications for IVC filter placement were DVT or PE in the presence of contraindications to anticoagulation therapy (perioperative, n = 58; CNS metastases, n = 20; thrombocytopenia, n = 7; bleeding, n = 61; others, n = 24; total, N = 170) or anticoagulation failure (recurrent PE, n = 6; recurrent DVT; n = 6; total N = 12). Filter placement complications (n = 6, 3%) included malposition (n = 3), migration (n = 1), arrhythmia (n = 1), and wound infection (n = 1), but no deaths. After filter placement, four patients developed a recurrent PE, and 11 patients developed a recurrent DVT. No significant postthrombotic complications were observed. CONCLUSION: IVC filter placement patients with advanced cancer and thrombotic complications is safe, well tolerated, and can offer effective therapy/prophylaxis with a low incidence of treatment failure.

Adolescent↗

Simultaneous retroperitoneal, thoracic, and cervical resection of postchemotherapy residual masses in patients with metastatic nonseminomatous germ cell tumors of the testis.

PURPOSE: We report our experience with simultaneous resection of residual masses above and below the diaphragm in patients with metastatic nomseminomatous germ cell tumor (NSGCT) of the testis. MATERIALS AND METHODS: Twenty-four patients underwent simultaneous resection of residual postchemotherapy masses in the retroperitoneum and chest, including three who also had radical neck dissection. All had been heavily pretreated with chemotherapy and five had undergone previous retroperitoneal lymph node dissections (RPLNDs). RESULTS: The combined procedure was performed with no mortality and low morbidity. The median length of the procedure was 5 hours 45 minutes, median blood loss 500 mL, and median length of hospital stay 9 days. Complications included one patient with chylous ascites and one with a prolonged air leak, both of which resolved with conservative management. Eighteen patients had similar pathologic findings in all sites: 13 with necrosis only and five with teratoma only. Six patients had discordant pathology in the abdomen and chest, including one with viable tumor in the chest only and two with viable tumor in the abdomen only. The overall actuarial 5-year survival rate for all patients was 79%. CONCLUSION: Simultaneous resection of neck, chest, and abdominal residual masses after chemotherapy for germ cell tumors is both a feasible and safe alternative to staged excision in selected patients who require surgical intervention at multiple sites and fulfills the objective of rendering patients disease-free in a single operative procedure.

Adolescent↗

Relationship of early postoperative dysrhythmias and long-term outcome after resection of non-small cell lung cancer.

STUDY OBJECTIVES: To determine whether supraventricular tachydysrhythmias (SVTs) occurring early after thoracic surgery for non-small cell lung cancer (NSCLC) are associated with poor long-term survival. DESIGN: Prospective, cohort. SETTING: Referral cancer center. PATIENTS: Seventy-eight patients undergoing resection of NSCLC. INTERVENTIONS: Examination of univariate and multivariate effects of factors that might influence long-term survival: advanced age, sex, perioperative chemotherapy, extent of pulmonary resection, tumor stage, and SVT occurrence. RESULTS: In this group of patients, 10 of 78 (13%) developed early postoperative SVT. Log-rank analysis showed SVT occurrence (p = 0.01), age of 70 years or older (p = 0.04), and perioperative chemotherapy (p = 0.005) to predict poor long-term survival. Multivariate Cox regression analysis identified SVT occurrence (p = 0.007; relative risk [RR], 2.8; 95% confidence interval [CI], 1.3 to 6.1) and perioperative chemotherapy (p = 0.004; RR, 2.6; 95% CI, 1.4 to 5.1) to be independently associated with decreased survival. No other clinical or laboratory characteristic tested differentiated those patients who did or did not develop postoperative SVT. CONCLUSIONS: Early SVT occurrence after resection of NSCLC is associated with poor long-term survival. Although the etiology for this is unclear, this intriguing observation, not previously reported (to our knowledge), may be used in larger trials examining the effects of these and other factors on survival from lung cancer surgery.

Adult↗

Management of malignant esophagorespiratory fistula.

For patients with malignant esophagorespiratory fistula, four important points need to be stressed: (1) once the diagnosis is made, treatment should be instituted immediately; (2) all treatment is palliative and directed at stopping soilage of the respiratory tract; (3) the type of therapy is dictated by the performance status of the patient at presentation; and (4) esophageal bypass offers the best palliation for those able to tolerate the procedure.

Bronchial Fistula↗

The treatment of patients with recurrent brain metastases. A retrospective analysis of 109 patients with nonsmall cell lung cancer.

BACKGROUND: Brain metastases represent a major source of morbidity in patients with cancer. METHODS: Treatment outcomes were analyzed retrospectively in 214 patients with brain metastases from nonsmall cell lung cancer (NSCLC) who underwent resection at Memorial Hospital (New York, NY) between January, 1976, and December, 1990. RESULTS: The study group included 109 patients (51%) with symptomatic recurrent brain tumors (median, 5.0 months after complete resection). Recurrence in the brain was at the original site in 62% of patients and at other sites in 38%. The median survival (MS) was 11.3 months in the recurrence group compared with 9.5 months (P < 0.5) in the nonrecurrence group (N = 105). Thirty-two patients had further surgery after recurrence; their median relapse time was 5.2 months. In these patients, survival (MS, 15.0 months) calculated from the time of their first operation, was significantly different (P < 0.001) from that of patients who did not undergo a second procedure (N = 77) (MS, 10.0 months). In the 32 patients who underwent reoperation, MS from the time of the second operation was 10 months, whereas the median interval from the first operation was 5 months (average, 5.7 months). Eight of these 32 patients had a third operation, after a median relapse time of 4 months; their MS was 42 months. There was a significant difference (P < 0.02) between the MS of 39 patients synchronously diagnosed with lung cancer and brain metastasis (MS, 9.0 months) and 70 metachronously diagnosed patients (MS, 14.6 months). Women (N = 55) survived longer than men (N = 54) (14.4 months vs. 9.7 months, P < 0.01). Univariate analysis showed that histology, disease stage, and completeness of resection of the primary tumor also affected survival (P < 0.02, P < 0.014, and P < 0.001, respectively). Although no significant difference was found between survival of patients with recurrence in the supratentorial space and patients with recurrence in the posterior fossa (MS, 11.4 months vs. 11.2 months, P < 0.13), no one from the latter subgroup survived 3 years. CONCLUSIONS: If technically feasible, further surgery is effective in prolonging the survival of patients with NSCLC who have recurring brain metastases.

Adult↗

Tumor necrosis factor alpha stimulates gluconeogenesis from alanine in vivo.

An increase in gluconeogenesis contributes to the cachexia seen in severe injury, sepsis, and malignancy by converting amino acids from skeletal muscle to glucose. Since tumor necrosis factor alpha (TNF alpha) may mediate this cachexia, we examined the effect of this cytokine on gluconeogenesis. Twenty-eight male Fischer rats were injected intraperitoneally with TNF alpha (250 micrograms/kg) or saline, and after 4 hours, isolated hepatocytes were obtained by in situ collagenase liver perfusion. Hepatocytes were incubated with alanine (10 mM), and rates of gluconeogenesis were determined. Plasma lactate, glucose, insulin, glucagon, cortisol, and amino acids were measured. TNF alpha administration resulted in a 50% increase in gluconeogenesis from alanine (P < 0.05) and a three-fold increase in plasma glucagon (P = 0.01). Total and glucogenic plasma amino acids decreased with TNF alpha injection (P < 0.05). In vivo TNF alpha causes an increase in hepatic gluconeogenesis associated with increased plasma glucagon.

Alanine↗

Perioperative growth hormone improves wound healing and immunologic function in rats receiving adriamycin.

Administration of perioperative growth hormone may reverse alterations in wound healing and immunologic function in animals receiving chemotherapy. F344 rats were randomized into three groups: Control (n = 12), Chemo (n = 13), and Chemo + GH (n = 12). Human growth hormone (GH) (3 mg/kg sc bid) was begun on Day 0 and continued for 2 weeks. On Day 7, all animals underwent a standardized midline laparotomy, gastrotomy, and placement of a subcutaneous wound sponge. In addition, a single dose of adriamycin (5 mg/kg i.v.) was administered to those animals receiving chemotherapy. On Day 12, right hindlimb footpads were challenged with 50 micrograms of dinitrochlorobenzene. On Day 14, bursting strengths of the laparotomy and gastrotomy were measured. The wound sponge and gastric anastomosis were analyzed for hydroxyproline (OH-Pro) content. Animal spleens were weighed and splenocytes harvested for NK cell activity. Delayed type hypersensitivity (DTH) is reported as percentage of hind-limb foot pad swelling (%FPS). Data are expressed as means +/- SD and comparisons by ANOVA. The laparotomy bursting strength (mm Hg) in the Chemo + GH group (81 +/- 14) was significantly higher than that in the Chemo group (66 +/- 15, P < 0.05). The anastomotic tissue OH-Pro levels (mumole/g dry tissue) in the Chemo + GH group (107.9 +/- 15.2) were significantly higher than those in the Chemo group (62.9 +/- 8.5, P < 0.001). GH increased splenic weights (mg) over those of Chemo (0.50 +/- 0.13 vs 0.37 +/- 0.05, P < 0.05). NK cell activity (% killing) was significantly elevated in the Chemo+GH group compared to that in Chemo.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

Energy depletion in the liver and in isolated hepatocytes of tumor-bearing animals.

Cancer cachexia has a great impact on morbidity and mortality in patients undergoing surgery. Failure to maintain lean tissue against tumor-induced hypermetabolism results in cumulative weight loss and ultimate failure of the host. Cellular free energy is among the factors that regulates metabolic pathways and may be altered in the tumor-bearing state. We studied in-vivo and in-vitro ATP levels and metabolic parameters in Fischer rats bearing a methylcholanthrene-induced sarcoma to elucidate the energy state. Tissue ATP was measured in freeze-clamped liver and muscle in 15 tumor-bearing rats (TBR) at different tumor burdens and their pair-fed controls (CTR) by bioluminescence assay. Plasma metabolites, hormones, and enzymes were determined in the same animals. Liver ATP level was lower in TBR with a 5% tumor burden: 3.07 +/- 0.56 (SE) nmole/mg tissue vs CTR: 5.33 +/- 0.60 (P < 0.05), 10% TBR: 2.48 +/- 0.54 vs CTR: 4.05 +/- 0.63 (n.s.), and 20% TBR: 1.91 +/- 0.21 vs CTR: 3.86 +/- 0.40 (P < 0.01). Muscle ATP was not different between TBR and CTR. This progressive loss of liver ATP was associated with decreased plasma insulin level (P < 0.001) and with increased alkaline phosphatase level (P < 0.01) by multiple regression. In vitro, hepatocytes were isolated from 8 TBR and 8 CTR by in-situ liver perfusion with collagenase and the cellular ATP was measured before and after 60 min incubation with glucogenic substrates. Hepatocytes from TBR decreased ATP by 42% (P < 0.05) in 10 mM lactate with higher gluconeogenesis, while control hepatocytes maintained the ATP.(ABSTRACT TRUNCATED AT 250 WORDS)

Adenosine Triphosphate↗

A region of primer binding variation at the D6S265 locus associated with HLA-A25 and HLA-A26 antigens.

D6S265 is a polymorphic dinucleotide repeat, mapped within 70 kb centromeric of HLA-A, on chromosome 6p21.3. While genotyping families for genetic linkage analysis, allele non-amplification resulting in apparent non-Mendelian inheritance was observed at the D6S265 locus in 15 individuals, on chromosomes carrying the HLA-A25 and HLA-A26 antigens. The D6S265 locus was sequenced in a variant individual homozygous for allele non-amplification, and in a non-HLA-A25/-A26 individual, homozygous for D6S265 allele 1. Five base changes were identified in the reverse primer binding region of the variant individual, effectively preventing annealing of the 3' primer to the template.

Base Sequence↗